Inhibition of P2X7 receptor ameliorates transient global cerebral ischemia/reperfusion injury via modulating inflammatory responses in the rat hippocampus

Background: neuroinflammation plays an important role in cerebral ischemia/reperfusion (i/r) injury. the p2x7 receptor (p2x7r) has been reported to be involved in the inflammatory response of many central nervous system diseases. however,the role of p2x7rs in transient global cerebral i/r injury remains unclear. the purpose of this study is to determine the effects of inhibiting the p2x7r in a rat model of transient global cerebral i/r injury,and then to explore the association between the p2x7r and neuroinflammation after transient global cerebral i/r injury.methods: immediately after infusion with the p2x7r antagonists brilliant blue g (bbg),adenosine 5′-triphosphate-2′,3′-dialdehyde (oxatp) or a-438079,20 minutes of transient global cerebral i/r was induced using the four-vessel occlusion (4-vo) method in rats. survival rate was calculated,neuronal death in the hippocampal ca1 region was observed using h & e staining,and dna cleavage was observed by deoxynucleotidyl transferase-mediated utp nick end labeling tunel). in addition,behavioral deficits were measured using the morris water maze,and rt-pcr and immunohistochemical staining were performed to measure the expression of il-1β,tnf-α and il-6,and to identify activated microglia and astrocytes.results: the p2x7r antagonists protected against transient global cerebral i/r injury in a dosage-dependent manner. a high dosage of bbg (10 μg) and a-0438079 (3 μg),and a low dosage of oxatp (1 μg) significantly increased survival rates,reduced i/r-induced learning memory deficit,and reduced i/r-induced neuronal death,dna cleavage,and glial activation and inflammatory cytokine overexpression in the hippocampus.conclusions: our study indicates that inhibiting p2x7rs protects against transient global cerebral i/r injury by reducing the i/r-induced inflammatory response,which suggests inhibition of p2x7rs may be a promising therapeutic strategy for clinical treatment of transient global cerebral i/r injury. © 2012 chu et al; licensee biomed central ltd.